Cancer
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21618
Browse
Browsing Cancer by Author "Grebennikov, Sarah"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Anti-Proliferative Effect of Copper Tolfenamic Acid in Neuroblastoma Cell Lines(2019-03-05) Basha, Riyaz; Sankpal, Umesh; Maram, Rajasekhar; Grebennikov, SarahAnti-Proliferative Effect of Copper Tolfenamic Acid in Neuroblastoma Cell Lines Sarah Grebennikov, Yazmin Hernandez, Rajasekhar Maram, Umesh T. Sankpal, and Riyaz Basha Background:Neuroblastoma (NB) is a neuroendocrine tumor of the sympathetic nervous system most commonly found in the adrenal medulla. It is the most common extracranial tumor in infants with an average age of onset of 1 year. While presentation in children over the age of 5 is rare, the prognosis is markedly worse due to the higher likelihood of an aggressive malignancy with metastasis to lymph nodes and bone marrow. Current treatment modalities include surgical resection, chemotherapy, radiotherapy, and autologous stem cell transplant. These treatments are highly efficacious, however there are several associated side effects. Specifically, chemotherapeutic side effects are dose dependent and can range from mild stomach pain to more severe and serious complications including hearing loss, myelosuppression, and neurotoxicity. To limit these side effects, we are investigating anti-cancer agents with limited side-effects. Copper Tolfenamic Acid (Cu-TA) is metallic complex of an anti-cancer Non-Steroidal Anti-inflammatory Drug, Tolfenamic acid which is known to inhibit anti-apoptotic protein, Survivin and inhibits cancer cell growth. Hypothesis: We hypothesize that Cu-TA down-regulates survivin and inhibits neuroblastoma cell growth more effectively than TA. Methods: NB cell lines, SMS-KCNR and LA155n cell lines (from ATCC) were treated with increasing concentrations of Cu-TA or TA (0, 5, 10, 20, 40 and 80 µM). CellTiter-Glo reagent was added to the 96-well plate, and readings were taken at 24 and 48 hours. Using this data, IC50 values were calculated using SigmaPlot software. The effect of Cu-TA on Survivin protein expression was measured using western blot analysis. Results: Cell viability data showed a dose dependent decrease due to Cu-TA treatment in both cell lines. Analysis of the Western Blot confirms that there was a decrease in the survivin protein in the cells treated with Cu-TA. Conclusion:These results demonstrate that Cu-TA is an inhibitor of survivin and more effective at inhibiting NB cancer cells than TA alone. Since survivin is associated with resistance to chemotherapy, if Cu-TA sensitizes NB cells to chemotherapy, it will help reduce the side effects of chemotherapy while maintaining the efficacy of treatment.Item Exploring Less Toxic Combination Treatment Options for Inducing Anti-Cancer Activity in Medulloblastoma Cells(2019-03-05) Smith, Kolton; Grebennikov, Sarah; Sankpal, Umesh; Bowman, W.; Basha, Riyaz; Schullek, MelissaPurpose.Medulloblastoma (MB) is the most common type of malignant pediatric brain cancer and is typically located in the posterior fossa. There are four subgroups within MB: Wnt, Sonic-Hedgehog, Group 3, and Group 4. Due to differences in pathology, signaling pathways, and gene expression, each subgroup is approached differently with respect to treatment, based upon differences in prognosis. Currently, the standard treatment approaches include surgical resection, radiotherapy, and chemotherapeutic agents such as etoposide, vincristine, and cisplatin. Survivors often suffer from severe long-term side effects including neurocognitive deficits and the potential for a future second neoplasm due to the tumorigenic potential of aggressive combination therapies. Because of these side-effects, there is an urgent need for effective and less toxic therapeutic strategies for the treatment of MB. Through prior research we have demonstrated the combination of etoposide alongside less toxic anti-cancer agents potentially increases anti-cancer activity in Ewing Sarcoma. We hypothesize that using a combination of etoposide with other sensitizing agents can also enhance the anti-cancer activity in MB cell lines. Methods. DAOY cells were cultured with increasing concentrations of Etoposide (ETO), Mithramycin-A (MIT), BNS-22 and Tolfenamic acid (TA) and the cell growth was monitored at 48 hours using CellTiter-Glo kit (luminescence cell viability assay). Dose-curves were then generated using sigma-plot software. After calculating the IC50 values for each agent, low dose of ETO (half of IC50 value) and IC50 value of other agents were tested for the combination treatment. Results. Overall, we observed decreased cell viability in a dose and time dependent manner for all tested agents. The IC50 values derived from the dose curves were 1 µg/ml for ETO, 33.3 nM for MIT, 15 µg/ml for TA, and 14.5 µM for BNS. The combination treatment using 0.5 µg/ml ETO and other agents (IC50 values) showed cell growth inhibition greater than any single agent in DAOY cells. The analysis revealed that the combination of ETO (0.5 µg/ml) plus BNS-22 was very effective. Conclusions: These preliminary data demonstrate promise in creating combination therapy of ETO with BNS-22 to treat DAOY cell lines. For better applications, similar experiments should be done with more cell lines representing various sub-groups of MB and to be confirmed by in vivoassays.